1. Field of the Invention
The invention described and claimed herein relates to psychopharmacologically active peptides, methods of preparing such compounds, and pharmaceutical compositions in a form suitable for therapeutic administration containing these peptides, and to those peptides suitable for the treatment of mental disorders, in which a stimulation of brain function is desired, e.g. for the treatment of senility and/or amnesia.
2. Description of Prior Art and Other Information
It is known from 157 NEUROPHARMACOL 4 (1965) that the nonapeptide derivative (Lys)-vasopressin zinc tannate possesses certain psychopharmacological properties when administered to rats, from which the hypophysis or the posterior lobe thereof has been removed. Specifically, this nonapeptide was alleged to be capable of inhibiting the extinction of the conditioned flight response. It is known that the extremely powerful pressor activity of vasopressin and its functional derivatives constitutes, however, a very unpleasant side-effect.
It is furthermore known to those in the art from U.S. Pat. No. 3,835,110 that a pentapeptide with the formula EQU H-L-Cys-L-Tyr-L-Phe-L-Glu(X)-L-Asp(X)-OH
or the dimer formed from this via a disulphide (S-S) bridge, inhibits the extinction of the conditioned avoidance response to at least the same extent as the nonapeptides above (specifically when on subcutaneous administration), but displays no pressor activity whatsoever. An objection to most peptides of this group is, however the extraordinarily poor solubility in most solvents, as a result of which purification, the usual performing of analyses and the pharmaceutical processing of these peptides is an extremely difficult and tiresome task.
Vasopressin polypeptide derivatives are furthermore prepared and shown in U.S. Pat. Nos. 3,299,036; 3,422,083 and 3,743,726. The compounds disclosed in U.S. Pat. No. 3,299,036 are particularly useful in the prophylaxis and therapy of parenchymatous bleeding. Further, the polypeptides of U.S. Pat. No. 3,422,083 have at least one .alpha. (-methylidene) group replaced by a nitrogen atom, and the compounds of U.S. Pat. No. 3,743,726 are octapeptides that stimulate the acquisition of the conditional avoidance response and inhibit its extinction. Representative patents directed to sulfonated/sulfated peptides are U.S. Pat. Nos. 3,579,494 and 3,705,140.